GeneBe

rs193922936

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002024.6(FMR1):​c.-120_-100delCGGCGGCGGCGGCGGCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000482 in 41,503 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., 0 hem., cov: 2)
Exomes 𝑓: 0.00016 ( 0 hom. 0 hem. )

Consequence

FMR1
NM_002024.6 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.66
Variant links:
Genes affected
FMR1 (HGNC:3775): (fragile X messenger ribonucleoprotein 1) The protein encoded by this gene binds RNA and is associated with polysomes. The encoded protein may be involved in mRNA trafficking from the nucleus to the cytoplasm. A trinucleotide repeat (CGG) in the 5' UTR is normally found at 6-53 copies, but an expansion to 55-230 repeats is the cause of fragile X syndrome. Expansion of the trinucleotide repeat may also cause one form of premature ovarian failure (POF1). Multiple alternatively spliced transcript variants that encode different protein isoforms and which are located in different cellular locations have been described for this gene. [provided by RefSeq, May 2010]
FMR1-AS1 (HGNC:39081): (FMR1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FMR1NM_002024.6 linkc.-120_-100delCGGCGGCGGCGGCGGCGGCGG 5_prime_UTR_variant Exon 1 of 17 ENST00000370475.9 NP_002015.1 Q06787-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FMR1ENST00000370475.9 linkc.-120_-100delCGGCGGCGGCGGCGGCGGCGG 5_prime_UTR_variant Exon 1 of 17 1 NM_002024.6 ENSP00000359506.5 Q06787-1

Frequencies

GnomAD3 genomes
AF:
0.0000284
AC:
1
AN:
35175
Hom.:
0
Cov.:
2
show subpopulations
Gnomad AFR
AF:
0.000103
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000158
AC:
1
AN:
6328
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
3418
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33
American (AMR)
AF:
0.00
AC:
0
AN:
6
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
33
East Asian (EAS)
AF:
0.00
AC:
0
AN:
6
South Asian (SAS)
AF:
0.00
AC:
0
AN:
97
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
42
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3
European-Non Finnish (NFE)
AF:
0.000168
AC:
1
AN:
5935
Other (OTH)
AF:
0.00
AC:
0
AN:
173
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000284
AC:
1
AN:
35175
Hom.:
0
Cov.:
2
AF XY:
0.00
AC XY:
0
AN XY:
5801
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.000103
AC:
1
AN:
9740
American (AMR)
AF:
0.00
AC:
0
AN:
2760
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
832
East Asian (EAS)
AF:
0.00
AC:
0
AN:
569
South Asian (SAS)
AF:
0.00
AC:
0
AN:
426
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
836
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
69
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
19299
Other (OTH)
AF:
0.00
AC:
0
AN:
465
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
89

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
2.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar for variant X:147912049 CGCGGCGGCGGCGGCGGCGGCG>C . It may be empty.

Other links and lift over

dbSNP: rs193922936; hg19: chrX-146993567; API